Cardiovascular disease can lead to myocardial infarction (Ml) and subsequent heart failure. There are currently a number of therapies aimed at preventing or treating heart failure post-MI. Only heart transplantation replaces infarcted myocardium to restore heart function, but there is a paucity of donor hearts and the incidence of cardiovascular disease continues to rise. A new and innovative option is the use of "heart patches" created in vitro for implantation in vivo. The research proposed in the independent phase of this award aims to address 2 critical issues pertaining to the function and eventual use of such heart patches: 1) the effect of a biomimetic culture environment on tissue morphology and function, and 2) the efficacy of myocardial equivalents biomimetically-engineered in vitro in restoring left ventricular function post-MI. The overall hypothesis of this work is that myocardium engineered in vitro in biomimetic culture conditions restores post-MI left ventricular function better than cell therapy-based methods of repair. The environment at the Tufts University uniquely positions me to address this hypothesis, as the world-renowned Tissue Engineering Research Center and Molecular Cardiology Research Institute are both located nearby. This environment will give me the opportunity to augment my already considerable background in tissue mechanics and tissue engineering methods with cardiac anatomy and physiology in health and disease and cardiac surgical techniques. The continuation of my career plan during the independent phase includes gaining more expertise in cell and tissue culture techniques and bioreactor development, while learning new skills in areas including cardiac surgical techniques and physiological evaluation in a rat model of Ml. The ultimate goal of the project is to leverage these skills to directly compare the efficacy of myocardial tissue engineered in vitro with current cell-therapy based methods of cardiac repair in restoring function to the left ventricle post-MI. This research is especially critical considering the continuing rise in incidence of heart disease. The results of this research may help elucidate design parameters that are critical to the creation of functional myocardium engineered in vitro and thus advance the concept of the "heart patch" closer to reality